Mechanical Ventilation (MV) is an invaluable, lifesaving therapy for patients with acute respiratory failure, but it must be individualized for each specific underlying physiologic derangement to maximize benefits and minimize harms.

Early optimization of ventilator settings should be aimed at counteracting respiratory and cardiac pathophysiology, fully supporting the work of breathing, preventing ventilator-induced lung injury, and minimizing PVA.

Improper MV management in the first few hours can be dangerous. It is not a “set it and forget it” intervention but instead requires frequent and careful attention to patient-ventilator interactions and close collaboration with the entire intensive care unit team, including bedside nurses and respiratory therapists, to ensure that ventilator settings are continually adjusted to meet patient needs.

Non–critical care-trained clinicians can use their comprehensive understanding of pathophysiology in combination with a practical understanding of MV in commonly encountered diseases to successfully manage acute respiratory failure in patients requiring MV.

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